CA2568995C - Construction d'une recombinaison d'adenovirus oncolytique exprimant de facon specifique un facteur immunomodulateur gm-csf dans des cellules tumorales et utilisations correspondantes - Google Patents
Construction d'une recombinaison d'adenovirus oncolytique exprimant de facon specifique un facteur immunomodulateur gm-csf dans des cellules tumorales et utilisations correspondantes Download PDFInfo
- Publication number
- CA2568995C CA2568995C CA2568995A CA2568995A CA2568995C CA 2568995 C CA2568995 C CA 2568995C CA 2568995 A CA2568995 A CA 2568995A CA 2568995 A CA2568995 A CA 2568995A CA 2568995 C CA2568995 C CA 2568995C
- Authority
- CA
- Canada
- Prior art keywords
- adenovirus
- recombinant
- cells
- gene
- sequence
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 241000701161 unidentified adenovirus Species 0.000 title claims abstract description 124
- 210000004881 tumor cell Anatomy 0.000 title claims abstract description 82
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 title claims abstract description 67
- 102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 title claims abstract description 46
- 230000000174 oncolytic effect Effects 0.000 title abstract description 42
- 238000010276 construction Methods 0.000 title abstract description 12
- 230000002519 immonomodulatory effect Effects 0.000 title abstract description 3
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 66
- 210000004027 cell Anatomy 0.000 claims description 108
- 241000700605 Viruses Species 0.000 claims description 59
- 108090000623 proteins and genes Proteins 0.000 claims description 47
- 230000001976 improved effect Effects 0.000 claims description 45
- 230000001105 regulatory effect Effects 0.000 claims description 36
- 108020004414 DNA Proteins 0.000 claims description 27
- 239000013612 plasmid Substances 0.000 claims description 24
- 238000004806 packaging method and process Methods 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 230000035897 transcription Effects 0.000 claims description 19
- 238000013518 transcription Methods 0.000 claims description 19
- 239000000835 fiber Substances 0.000 claims description 18
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 claims description 15
- 108091034057 RNA (poly(A)) Proteins 0.000 claims description 15
- 239000012528 membrane Substances 0.000 claims description 15
- 238000011144 upstream manufacturing Methods 0.000 claims description 11
- 241000701124 Human adenovirus 35 Species 0.000 claims description 10
- 108700005075 Regulator Genes Proteins 0.000 claims description 9
- 238000002347 injection Methods 0.000 claims description 9
- 239000007924 injection Substances 0.000 claims description 9
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 238000002512 chemotherapy Methods 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 238000002744 homologous recombination Methods 0.000 claims description 2
- 230000006801 homologous recombination Effects 0.000 claims description 2
- 238000001959 radiotherapy Methods 0.000 claims description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 238000001415 gene therapy Methods 0.000 abstract description 7
- 239000012634 fragment Substances 0.000 description 27
- 230000000694 effects Effects 0.000 description 25
- 230000003362 replicative effect Effects 0.000 description 23
- 230000003612 virological effect Effects 0.000 description 22
- 238000011160 research Methods 0.000 description 18
- 108010017842 Telomerase Proteins 0.000 description 17
- 201000011510 cancer Diseases 0.000 description 14
- 230000028993 immune response Effects 0.000 description 12
- 244000309459 oncolytic virus Species 0.000 description 12
- 239000013598 vector Substances 0.000 description 12
- 238000012163 sequencing technique Methods 0.000 description 10
- 230000000259 anti-tumor effect Effects 0.000 description 8
- 239000002299 complementary DNA Substances 0.000 description 8
- 210000000130 stem cell Anatomy 0.000 description 8
- 108700005077 Viral Genes Proteins 0.000 description 7
- 239000003623 enhancer Substances 0.000 description 7
- 238000002703 mutagenesis Methods 0.000 description 7
- 231100000350 mutagenesis Toxicity 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 230000005758 transcription activity Effects 0.000 description 7
- 229920001817 Agar Polymers 0.000 description 6
- 101150076489 B gene Proteins 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 108020004999 messenger RNA Proteins 0.000 description 6
- 108091008146 restriction endonucleases Proteins 0.000 description 6
- 238000012552 review Methods 0.000 description 6
- 101000961414 Homo sapiens Membrane cofactor protein Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 239000013592 cell lysate Substances 0.000 description 5
- 230000001276 controlling effect Effects 0.000 description 5
- 230000002950 deficient Effects 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 230000001404 mediated effect Effects 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 238000001890 transfection Methods 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- ABAFKQHGFDZEJO-UHFFFAOYSA-N 4,6,6-trimethylbicyclo[3.1.1]heptane-4-carbaldehyde Chemical compound C1C2C(C)(C)C1CCC2(C)C=O ABAFKQHGFDZEJO-UHFFFAOYSA-N 0.000 description 4
- 101000655352 Homo sapiens Telomerase reverse transcriptase Proteins 0.000 description 4
- 241001135569 Human adenovirus 5 Species 0.000 description 4
- 102100039373 Membrane cofactor protein Human genes 0.000 description 4
- 241000218633 Pinidae Species 0.000 description 4
- 206010060862 Prostate cancer Diseases 0.000 description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- 102000040945 Transcription factor Human genes 0.000 description 4
- 102100024026 Transcription factor E2F1 Human genes 0.000 description 4
- 101710138750 Transcription factor E2F1 Proteins 0.000 description 4
- 239000008272 agar Substances 0.000 description 4
- 238000000137 annealing Methods 0.000 description 4
- 238000012258 culturing Methods 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 210000000605 viral structure Anatomy 0.000 description 4
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 101150066038 E4 gene Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 108010084938 adenovirus receptor Proteins 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000022534 cell killing Effects 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 239000002773 nucleotide Substances 0.000 description 3
- 125000003729 nucleotide group Chemical group 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 230000005030 transcription termination Effects 0.000 description 3
- 229960005486 vaccine Drugs 0.000 description 3
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 108010093502 E2F Transcription Factors Proteins 0.000 description 2
- 102000001388 E2F Transcription Factors Human genes 0.000 description 2
- 102000015699 E2F1 Transcription Factor Human genes 0.000 description 2
- 108010063774 E2F1 Transcription Factor Proteins 0.000 description 2
- 101150071673 E6 gene Proteins 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 241000598171 Human adenovirus sp. Species 0.000 description 2
- 239000005089 Luciferase Substances 0.000 description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 2
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 238000004166 bioassay Methods 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 210000000234 capsid Anatomy 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000012411 cloning technique Methods 0.000 description 2
- 238000005094 computer simulation Methods 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 230000001461 cytolytic effect Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000012407 engineering method Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 238000001976 enzyme digestion Methods 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 230000002601 intratumoral effect Effects 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 210000002901 mesenchymal stem cell Anatomy 0.000 description 2
- 238000009126 molecular therapy Methods 0.000 description 2
- 238000011580 nude mouse model Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 210000001082 somatic cell Anatomy 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 230000037455 tumor specific immune response Effects 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 238000000316 virotherapy Methods 0.000 description 2
- 101150084750 1 gene Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010005003 Bladder cancer Diseases 0.000 description 1
- 108090000565 Capsid Proteins Proteins 0.000 description 1
- 102100023321 Ceruloplasmin Human genes 0.000 description 1
- 206010008342 Cervix carcinoma Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 108091035710 E-box Proteins 0.000 description 1
- 101150082674 E2 gene Proteins 0.000 description 1
- 101710145505 Fiber protein Proteins 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101001093139 Homo sapiens MAU2 chromatid cohesion factor homolog Proteins 0.000 description 1
- 101000904152 Homo sapiens Transcription factor E2F1 Proteins 0.000 description 1
- 241000341655 Human papillomavirus type 16 Species 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 102100036309 MAU2 chromatid cohesion factor homolog Human genes 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100490488 Mus musculus Add3 gene Proteins 0.000 description 1
- 108700019961 Neoplasm Genes Proteins 0.000 description 1
- 102000048850 Neoplasm Genes Human genes 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 108010076570 Recoverin Proteins 0.000 description 1
- 102100034572 Recoverin Human genes 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
- HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000030741 antigen processing and presentation Effects 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 229940022399 cancer vaccine Drugs 0.000 description 1
- 238000009566 cancer vaccine Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 201000010881 cervical cancer Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 108010010892 coxsackievirus B receptor Proteins 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 241001493065 dsRNA viruses Species 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 238000009585 enzyme analysis Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000004992 fission Effects 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 102000050313 human E2F1 Human genes 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000001902 propagating effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000003584 silencer Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/193—Colony stimulating factors [CSF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10332—Use of virus as therapeutic agent, other than vaccine, e.g. as cytolytic agent
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10341—Use of virus, viral particle or viral elements as a vector
- C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2810/00—Vectors comprising a targeting moiety
- C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
- C12N2810/60—Vectors comprising as targeting moiety peptide derived from defined protein from viruses
- C12N2810/6009—Vectors comprising as targeting moiety peptide derived from defined protein from viruses dsDNA viruses
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/36—Vector systems having a special element relevant for transcription being a transcription termination element
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
- C12N2840/203—Vectors comprising a special translation-regulating system translation of more than one cistron having an IRES
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Engineering & Computer Science (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB200410046237XA CN100361710C (zh) | 2004-06-07 | 2004-06-07 | 肿瘤细胞专一表达免疫调节因子gm-csf的溶瘤性腺病毒重组体的构建及其应用 |
| CN200410046237.X | 2004-06-07 | ||
| PCT/CN2004/001321 WO2005121343A1 (fr) | 2004-06-07 | 2004-11-19 | Construction d'une recombinaison d'adenovirus oncolytique exprimant de facon specifique un facteur immunomodulateur gm-csf dans des cellules tumorales et utilisations correspondantes |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| CA2568995E CA2568995E (fr) | 2005-12-22 |
| CA2568995A1 CA2568995A1 (fr) | 2005-12-22 |
| CA2568995C true CA2568995C (fr) | 2012-02-21 |
Family
ID=35503069
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2568995A Active CA2568995C (fr) | 2004-06-07 | 2004-11-19 | Construction d'une recombinaison d'adenovirus oncolytique exprimant de facon specifique un facteur immunomodulateur gm-csf dans des cellules tumorales et utilisations correspondantes |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US7951585B2 (fr) |
| EP (1) | EP1767642B1 (fr) |
| JP (1) | JP4874247B2 (fr) |
| CN (1) | CN100361710C (fr) |
| BR (1) | BRPI0418805B8 (fr) |
| CA (1) | CA2568995C (fr) |
| DK (1) | DK1767642T3 (fr) |
| ES (1) | ES2466415T3 (fr) |
| PL (1) | PL1767642T3 (fr) |
| PT (1) | PT1767642E (fr) |
| RU (1) | RU2361611C2 (fr) |
| WO (1) | WO2005121343A1 (fr) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008527981A (ja) * | 2005-01-25 | 2008-07-31 | アポロ ライフ サイエンシズ リミテッド | 治療目的および診断目的のためにパラメーターにより選択されたｇｍ−ｃｓｆ、ｉｌ−３、ｉｌ−４、ｉｌ−５、ならびにそのキメラ |
| CA2995971A1 (fr) | 2005-03-25 | 2006-10-05 | Regeneron Pharmaceuticals, Inc. | Formulations d'antagonistes du facteur vegf |
| JP5216002B2 (ja) | 2006-06-16 | 2013-06-19 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | 硝子体内投与に適したｖｅｇｆアンタゴニスト製剤 |
| JP2008048621A (ja) * | 2006-08-22 | 2008-03-06 | Chiba Prefecture | キメラ型アデノウイルスとその作製方法並びにそれを用いた医薬 |
| CN101391104B (zh) * | 2007-09-21 | 2010-10-06 | 成都康弘生物科技有限公司 | 肿瘤细胞专一表达免疫调节因子gm-csf的溶瘤性腺病毒重组体的新用途 |
| CN103221423B (zh) | 2010-09-24 | 2015-09-30 | 昂克斯治疗有限公司 | 溶瘤腺病毒载体及与其相关的方法和用途 |
| WO2012088446A1 (fr) | 2010-12-22 | 2012-06-28 | Board Of Trustees Of The Leland Stanford Junior University | Super-agonistes et antagonistes de l'interleukine-2 |
| EP3763379A1 (fr) | 2011-01-13 | 2021-01-13 | Regeneron Pharmaceuticals, Inc. | Utilisation d'un antagoniste du vegf pour traiter des troubles oculaires angiogéniques |
| CN102174479B (zh) * | 2011-03-02 | 2013-04-03 | 北京锤特生物科技有限公司 | 靶向性治疗人肿瘤的溶肿瘤腺病毒及其应用 |
| JP5971599B2 (ja) * | 2011-08-23 | 2016-08-17 | 国立研究開発法人医薬基盤・健康・栄養研究所 | 制限増殖型アデノウイルス |
| US9624476B2 (en) | 2011-08-23 | 2017-04-18 | National Institute Of Biomedical Innovation | Conditionally replicating adenovirus |
| FI123955B (en) | 2011-11-25 | 2014-01-15 | Oncos Therapeutics Ltd | Oncolytic adenovirus |
| CA2865642C (fr) * | 2012-03-14 | 2021-10-26 | Salk Institute For Biological Studies | Diagnostic de tumeur adenovirale |
| US9017672B2 (en) | 2012-05-11 | 2015-04-28 | Immunicum Aktiebolag | Hexon Tat-PTD modified adenovirus and uses thereof |
| EP2971008B1 (fr) | 2013-03-14 | 2018-07-25 | Salk Institute for Biological Studies | Compositions d'adénovirus oncolytiques |
| KR20160002848A (ko) * | 2013-03-24 | 2016-01-08 | 오이신 바이오테크놀로지스 | 표적 세포 내에서 치료적 단백질의 표적화된 생산을 위한 시스템 및 방법 |
| WO2014171526A1 (fr) * | 2013-04-17 | 2014-10-23 | 国立大学法人九州大学 | Virus coxsackie génétiquement modifié |
| LT3021859T (lt) | 2013-10-25 | 2018-06-11 | Psioxus Therapeutics Limited | Onkolitiniai adenovirusai su heterologiniais genais |
| RU2682762C2 (ru) * | 2013-11-27 | 2019-03-21 | Общество С Ограниченной Ответственностью "Панацела Лабс" | Улучшенный вектор, экспрессирующий toll-подобный рецептор и агонист, и применение в терапии рака |
| EP3391892A1 (fr) | 2015-04-30 | 2018-10-24 | Psioxus Therapeutics Limited | Adénovirus oncolytique codant une protéine b7 |
| JP7064437B2 (ja) | 2015-12-17 | 2022-05-10 | サイオクサス セラピューティクス リミテッド | 抗ｔｃｒ複合体抗体又は断片をコードするｂ群アデノウイルス |
| KR102471633B1 (ko) | 2016-02-23 | 2022-11-25 | 솔크 인스티튜트 포 바이올로지칼 스터디즈 | 바이러스 동역학에 미치는 영향 최소화를 위한 치료용 아데노바이러스의 외인성 유전자 발현 |
| WO2017147265A1 (fr) | 2016-02-23 | 2017-08-31 | Salk Institute For Biological Studies | Dosage à haut débit pour mesurer la cinétique de réplication d'un adénovirus |
| CN110062630A (zh) | 2016-12-12 | 2019-07-26 | 萨克生物研究学院 | 肿瘤靶向合成腺病毒及其用途 |
| CA3047140A1 (fr) | 2017-01-09 | 2018-07-12 | Oisin Biotechnologies | Constructions genetiques pour l'expression de proteines therapeutiques dans des cellules ciblees |
| CA3067909A1 (fr) * | 2017-06-19 | 2018-12-27 | Medicenna Therapeutics Inc. | Utilisations et procedes pour des superagonistes et agonistes d'il-2 et des fusions de ceux-ci |
| SG11202005509YA (en) * | 2017-12-13 | 2020-07-29 | Genemedicine Co Ltd | Recombinant adenoviruses and stem cells comprising same |
| JP2021526505A (ja) | 2018-04-18 | 2021-10-07 | オイシン バイオテクノロジーズ，インク． | 治療用タンパク質の標的細胞に特異的な産生のための、および、標的細胞に関連する疾患、疾病、または障害の処置のための、融合性脂質ナノ粒子、および、融合性脂質ナノ粒子の製造方法と使用方法 |
| KR20210093303A (ko) | 2018-11-21 | 2021-07-27 | 메이오 파운데이션 포 메디칼 에쥬케이션 앤드 리써치 | 아데노바이러스 및 아데노바이러스의 사용 방법 |
| WO2020166727A1 (fr) * | 2019-02-12 | 2020-08-20 | 国立大学法人大阪大学 | Virus oncolytique utilisant l'adénovirus humain de type 35 comme base |
| JP7381604B2 (ja) | 2019-04-29 | 2023-11-15 | メイヨ・ファウンデーション・フォー・メディカル・エデュケーション・アンド・リサーチ | 癌を治療するための多価ｐｄ－ｌ１結合化合物 |
| JP2023519926A (ja) * | 2020-03-23 | 2023-05-15 | キュリジン カンパニー，リミテッド | 二重特異性核酸分子を含む抗癌ウイルスの構造 |
| RU2753742C1 (ru) * | 2020-10-16 | 2021-08-24 | Федеральное государственное автономное образовательное учреждение высшего образования "Новосибирский национальный исследовательский государственный университет" (Новосибирский государственный университет, НГУ) | Рекомбинантный штамм Ad6-hTERT-GMCSF, содержащий встройку промотора теломеразы человека hTERT, а также гена гранулоцитарно-макрофагального колониестимулирующего фактора человека, обладающий избирательной цитолитической активностью против теломераза-положительных опухолевых клеток и экспрессирующий активный человеческий гранулоцитарно-макрофагальный колониестимулирующий фактор |
| CN115029325A (zh) * | 2021-03-08 | 2022-09-09 | 南京惟亚德生物医药有限公司 | 一种重组溶瘤腺病毒及其应用 |
| CN113444730A (zh) * | 2021-03-17 | 2021-09-28 | 昆明市延安医院 | 一种原发性肝细胞klotho基因转导干细胞筛选构建方法 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7592317B1 (en) * | 1994-08-11 | 2009-09-22 | The University Of Chicago | Constitutive gene expression in conjuction with ionizing radiation |
| AU3551195A (en) | 1994-09-23 | 1996-04-09 | Somatix Therapy Corporation | Chimeric adenovirus for gene delivery |
| US6020191A (en) | 1997-04-14 | 2000-02-01 | Genzyme Corporation | Adenoviral vectors capable of facilitating increased persistence of transgene expression |
| US5891432A (en) * | 1997-07-29 | 1999-04-06 | The Immune Response Corporation | Membrane-bound cytokine compositions comprising GM=CSF and methods of modulating an immune response using same |
| US6348450B1 (en) | 1997-08-13 | 2002-02-19 | The Uab Research Foundation | Noninvasive genetic immunization, expression products therefrom and uses thereof |
| AU762493B2 (en) | 1998-03-11 | 2003-06-26 | Board Of Regents, The University Of Texas System | Induction of apoptic or cytotoxic gene expression by adenoviral mediated gene codelivery |
| CN1298451A (zh) * | 1998-04-24 | 2001-06-06 | 昂尼克斯药物公司 | 用于治疗疾病的腺病毒载体 |
| US6627190B2 (en) | 1999-07-12 | 2003-09-30 | Saint Louis University | Recombinant adenovirus vectors that are replication-competent in tert-expressing cells |
| GB9916851D0 (en) * | 1999-07-20 | 1999-09-22 | Univ Wales Bangor | Manipulation of particles in liquid media |
| DK1230378T3 (da) | 1999-11-15 | 2007-10-08 | Onyx Pharma Inc | Et onkolytisk adenovirus |
| DE60116513T2 (de) * | 2000-08-10 | 2006-09-21 | Crucell Holland B.V. | Adenovirenvektoren zur transduktion der chondrozyten |
| US6713055B2 (en) | 2000-11-27 | 2004-03-30 | Geron Corporation | Glycosyltransferase vectors for treating cancer |
| IL152420A0 (en) * | 2001-02-23 | 2003-05-29 | Novartis Ag | Novel oncolytic adenoviral vectors |
| CN1177053C (zh) | 2001-04-13 | 2004-11-24 | 上海华康生物技术有限公司 | 靶向性、高表达人粒细胞巨噬细胞集落刺激因子的重组腺病毒及其制法和用途 |
| US6905678B2 (en) * | 2001-07-07 | 2005-06-14 | Crucell Holland B.V. | Gene delivery vectors with cell type specificity for mesenchymal stem cells |
| CN1195056C (zh) * | 2001-07-12 | 2005-03-30 | 钱其军 | 一种在肿瘤细胞中特异性增殖及高效表达抗癌基因的重组病毒及其构建方法 |
| US20030099616A1 (en) * | 2001-07-25 | 2003-05-29 | Irving John M. | Dual specificity tumor killing vectors driven by the telomerase promoter |
| US20030082722A1 (en) | 2001-08-08 | 2003-05-01 | Bingliang Fang | Method for amplifying expression from a cell specific promoter |
| JP3867968B2 (ja) * | 2002-07-08 | 2007-01-17 | 関西ティー・エル・オー株式会社 | 腫瘍細胞において選択的に増殖する腫瘍融解ウイルス |
| CN1259106C (zh) * | 2002-12-23 | 2006-06-14 | 中国科学院上海生命科学研究院 | 一种抗癌靶向基因病毒药物的制备方法 |
| ES2292271B1 (es) | 2004-05-20 | 2009-02-16 | Proyecto De Biomedicina Cima, S.L. | Un vector hibrido adenovirus-alfavirus para la administracion eficaz y expresion de genes terapeuticos en celulas tumorales. |
-
2004
- 2004-06-07 CN CNB200410046237XA patent/CN100361710C/zh not_active Expired - Lifetime
- 2004-11-19 US US11/628,760 patent/US7951585B2/en active Active
- 2004-11-19 ES ES04797352.4T patent/ES2466415T3/es active Active
- 2004-11-19 DK DK04797352.4T patent/DK1767642T3/da active
- 2004-11-19 EP EP04797352.4A patent/EP1767642B1/fr active Active
- 2004-11-19 PT PT47973524T patent/PT1767642E/pt unknown
- 2004-11-19 WO PCT/CN2004/001321 patent/WO2005121343A1/fr active Search and Examination
- 2004-11-19 BR BRPI0418805A patent/BRPI0418805B8/pt active IP Right Grant
- 2004-11-19 JP JP2007526164A patent/JP4874247B2/ja active Active
- 2004-11-19 CA CA2568995A patent/CA2568995C/fr active Active
- 2004-11-19 PL PL04797352T patent/PL1767642T3/pl unknown
- 2004-11-19 RU RU2006146665/13A patent/RU2361611C2/ru active
Also Published As
| Publication number | Publication date |
|---|---|
| PL1767642T3 (pl) | 2014-08-29 |
| BRPI0418805B1 (pt) | 2021-01-26 |
| US7951585B2 (en) | 2011-05-31 |
| RU2361611C2 (ru) | 2009-07-20 |
| JP4874247B2 (ja) | 2012-02-15 |
| BRPI0418805B8 (pt) | 2021-05-25 |
| EP1767642A1 (fr) | 2007-03-28 |
| PT1767642E (pt) | 2014-06-03 |
| WO2005121343A1 (fr) | 2005-12-22 |
| EP1767642B1 (fr) | 2014-04-23 |
| JP2008501349A (ja) | 2008-01-24 |
| CN100361710C (zh) | 2008-01-16 |
| CN1706955A (zh) | 2005-12-14 |
| CA2568995E (fr) | 2005-12-22 |
| DK1767642T3 (da) | 2014-05-26 |
| ES2466415T3 (es) | 2014-06-10 |
| RU2006146665A (ru) | 2008-07-20 |
| EP1767642A4 (fr) | 2008-06-25 |
| US20100047208A1 (en) | 2010-02-25 |
| BRPI0418805A (pt) | 2007-10-16 |
| CA2568995A1 (fr) | 2005-12-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2568995C (fr) | Construction d'une recombinaison d'adenovirus oncolytique exprimant de facon specifique un facteur immunomodulateur gm-csf dans des cellules tumorales et utilisations correspondantes | |
| ES2258265T3 (es) | Vectores de replicacion con especificidad tisular. | |
| EP1749098A2 (fr) | Adenovirus chimeres a utiliser dans le traitement du cancer | |
| Rivera et al. | Mode of transgene expression after fusion to early or late viral genes of a conditionally replicating adenovirus via an optimized internal ribosome entry site in vitro and in vivo | |
| US20080118470A1 (en) | Oncolytic adenoviral vectors encoding GM-CSF | |
| JP4386971B2 (ja) | スプライシング配列を含んでなる組換えアデノウイルスベクター | |
| EP3440213A1 (fr) | Vecteurs adénoviraux | |
| IL135983A (en) | Adenoviral vectors and a method for reducing the frequency of inter- or intra-molecular homologous recombination between chromosomal nucleic acids and extra-chromosomal nucleic acids | |
| AU772963B2 (en) | Adenoviral vectors for treating disease | |
| US20060257370A1 (en) | Adenoviral vectors for treating diseases | |
| EP3305904B1 (fr) | Promoteur dérivé de poxvirus, et vecteur le comprenant | |
| ES2239841T3 (es) | Vectores adenovirales quimericos. | |
| AU781775B2 (en) | Adenoviral vectors for treating disease | |
| CN113774031B (zh) | 一种复制型人腺病毒及其应用 | |
| WO2002053760A2 (fr) | Virus cytolytiques chimeres destines au traitement du cancer | |
| AU2005209653B2 (en) | Adenoviral vectors for treating disease |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| NARE | Reissued |
Effective date: 20131224 |
|
| NARE | Reissued |
Effective date: 20131224 |
|
| NARE | Reissued |
Effective date: 20131224 |